Process for preparation of terpene flavorants

ABSTRACT

A process for preparing sinensal by the ozonization of beta farnesene and reduction of the ozonolysis product to obtain sinensal, which is suitable as a flavor-inparting agent of orange aroma.

United States Patent H 1 3,699,169 Bertele et al. 51 Oct. 17, 1972 [54] PROCESS FOR PREPARATION OF [56] References Cited TERPENE FLAVORA NTS OTHER PUBLICATIONS [72] Inventors: Erhard Bertele, Diibendorf; Peter v s n near wetzikon both Bailey, P. 8., Chemical Reviews, Vol. 58, 1968, pages Switzerland 988- 991' 1 J c s v I 65 1943 2183 [73] Assignee: Givaudan Corporation, Delawanna, at A. o. pages Pinder, A. R., The Chemistry of the Terpenes, 1960, [22] Filed: Sept. 5, 1968 page 115. [2U App! 757772 Primary Examiner-Leon Zitver Assistant Examiner-R. H. Liles [30] Foreign Application Priority Data Attorney-Cifelli and Behr l I 0 Sept 5, 1967 Switzerland 13041167 ABSTRACT [52] 0.8. CI ..260/604 R, 260/339, 260/413, A process for preparing sinensa] by the ozonization of 260/603 HF, 99/140 R, 260/632 R, 260/60 beta farnesene and reduction of the ozonolysis 260/410 product to obtain sinensal, which is suitable as a [5 l 1 C070 orange aroma [58] Field of Search ..260/601, 60] R, 604 R 2 Claims, No Drawings PROCESS FOR PREPARATION OF TERPENE FLAVORANTS SUMMARY OF THE INVENTION DETAILED DESCRIPTION OF THE INVENTION The invention is concerned with a process for the manufacture of compounds of the general formula R r I wherein R signifies a CH OI-I, Cl-IO or COOH group, and the broken lines represent a double bond emanating from C-atom 3, and the conversion thereof into aor B- sinensal of the formula I OHC IV The process in accordance with the invention for the manufacture of compounds of formula I is characterized in that a compound of the formula is ozonized and the ozonization product which is obtained is decomposed to give a compound of general formula I.

a-Farnesene or B-farnesene or a mixture of both can be used as the starting material of formula II.

Formulas I, II and IV are meant to also include the structures which are cis-trans isomeric to the illustrated structures. Thus, for example, formula I is meant to denote both the cis and the trans forms of aor B- sinensal.

The ozonization of the tetraene II surprisingly proceeds selectively, since the conjugated double bond practically does not enter into reaction with the ozone.

The ozonization can be undertaken according to methods known per se by bringing ozone-containing gas into contact with the tetraene which is to be ozonized, conveniently by introduction of the gas into a preferably dilute solution of the tetraene. Presently preferred solvents are those which are inert to ozone,- or at least display greater stability than the substance which is to be ozonized; for example, alkanes such as hexane, petroleum ether, cyclohexane; benzene and its derivatives; halogenated hydrocarbons such as carbon tetrachloride, chloroform, methylene chloride, methyl chloride, ethyl. chloride, ethyl bromide; esters such as formic acid or acetic acid esters (ethyl acetate); ketones such as acetone or methyl ethyl ketone; ethers such as dimethyl ether, diethyl ether, tetrahydrofuran; acid anhydrides such as acetic anhydride; acid amides such as formamide, dimethylformamide; nitromethane etc. Among other solvents which may be used are those which can enter into reaction with the ozonide which is primarily formed: carboxylic acids (for example, formic acid, acetic acid, propionic acid); alcohols such as methanol, ethanol, propanol; water in admixture with acetone. Best suited are solvents which are able to hold the ozonization products in solution. Furthermore, lowboiling solvents are to be preferred, since these are usually readily separable from the reaction products. Particularly suitable solvents are, for example: methyl chloride, chloroform, carbon tetrachloride, benzene, acetone, ethyl acetate, methanol.

The concentration of the solution which is to be ozonized can vary within wide limits. In general, dilute solutions give better yields. On practical grounds, 5-20 percent solutions will usually be used.

Conveniently, not more than about 1 mol equivalent of ozone is allowed to act on the tetraene II, in order to avoid an oxidation of the reaction products. Normally, an oxygen stream with an ozone content of about 2-l0 percent is used. However, more dilute and more concentrated ozone mixtures also may be employed. If desired, oxygen-free ozone'( as the gas or as a solution) may be used. 1 I

The ozonization is advantageously carried out at temperatures below room temperature, conveniently at temperatures below 0 C. Particularly good yields are obtained at temperatures within the range of about 50 to C.

The cleavage of the primarily obtained ozonization products to the compounds of general formula I can be undertaken according to methods known per se. Al-

cohols (formula I; R=CH OI-I) may be obtained bytreating the ozonization product which is'formed with a powerful reducing agent, of the type known to be suitable to reduce ozonides to alcohols, such as a complex metal hydride (e.g. lithium aluminum hydride or sodium borohydride), or with hydrogen, catalytically-activated by noble or transition metals (e.g. palladium,

platinum) or complexes of such metals (as for example, tris-triphenyl-phosphine-rhodium chloride).

Aldehydes (formula I: R=CI-IO) can be obtained from the ozonization products by treatment with a mild reducing agent; of the type known to be suitable'to reduce ozonides to aldehydes, for example, an iodide (e.g. sodium or potassium iodide), sulphite, bisulphite (e.g. sodium bisulphite), with formaldehyde, sulphur dioxide, pyridine, hydrazine hydrate, with a sulphide (e.g. dimethyl sulphide), with hydroquinone, zinc or magnesium in acidic solution, with Raney-nickel, phosphorus (III)-compounds (e.g. phosphines such as triphenylphosphine, tri-loweralkyl-phosphites such as trimethylphosphite), hydrogen [catalytically activated by noble-or transition metals orv complexes thereof examples os such systems are Ptll-l Pd/C/I-l Carboxylic acids (formula I: R=COOH) may be obtained from the primary products of the ozonization by treatment with an oxidizing agent; for example, by treatment with potassium permanganate, hydrogen peroxide, peracids, chromic acid, oxygen (catalyzed by manganese or silver salts). With aluminum hydrides (such as, for example, lithium aluminum hydride), the acids can be reduced directly or, if desired, in the form of their esters to the corresponding alcohols in a manner known per se. Likewise, the acids may be converted via the acid chlorides into the amides (e.g. the

M \I p v aluminum hydride or lithium .diethoxy aluminum,

hydride). The esters derived from the acids may also be directly converted into the aldehydes at lower temperature.

The alcohols, aldehydes or carboxylic acids obtained by ozonization of the tetraene II and by subsequent reductive or oxidative cleavage of the ozonization products are new compounds which can be used as interniediate products. for the manufacture of compounds having orange aroma, especially of the B- sinensaLoccurring in orange oil (Citrus sinensis) (trans-fisinensal: 2,6-dimethyl--methylene-2t, 6t, 1 1- dodecatrienal), 'of isomers thereof (cis-B-sinensal, cis and transa-sinensal), as well as-of analogues such as, for example, the corresponding alcohols or acid esters which are likewise distinguished by particular aroma notes (flavor after the manner of citrus fruits), on the basis of which the compounds can be used for aromatization, for example, of drinks, in the manner of the well-known flavorant, aldehyde C-lO.

Thus, for example, the aldehyde la which is'obtainable from trans B-farnesene (Ila) can be converted into trans fl-sinensal lVa as shown in the followingscheme:

' SCHEME l w no He Ia M Pawn I I CHO l m QOOR vI CHO - CHzOH IVa VII cording to Wittig with a phosphorane of formula Ill- (wherein Ph signifies a phenyl group).

According to the other variant, the aldehyde la which is obtained is reacted according to Wittig with a phosphorane of formula V (wherein Ph has the above significance and R represents a lower. alkyl group to give the tetraene ester VI, this ester is reduced to the (correspondingv tetraene alcoholv VII according 1 to methods which are knowper se (e.g. with lithium aluminum hydride), and finally the alcohol obtained is 0x idized to the corresponding aldehyde (trans-,B-sinensal lVa) according to methods which are known per se EXAMPLEI 12.5 g-(6l.3 mmol) oftra'ns B-farnesene are dissolvedin 1 20 ml of absolute methanol. 49 mmol of are ozone are then introduced during 2 hours at -90. It is then briefly flushed with N, and the reaction mixture treated at0 with 6.75 ml (92 mmol) of dimethyl sulphiderAfter stirring for 1.1/2 hours at 0, the methanol is distilled off and the residue chromatographed on the 10-fold amount of silica gel (Merck 0.05-0.2). By elution with hexane, there are obtained 64 g of starting material (trans B-farnesene). Elution with benzene yields the triene aldehyde 4-methyl-8-methylene-4t, 9-

decadienal), which'for the purpose of purification is distilled in the bulb tube. (B.p. /0.1 mm; n 1.4887); lR-bands at 1730s; 1600 m; 900s cm.

EXAMPLE 2 mg (0.98 mmol) of the trans triene aldehyde la (4-methyl-8-rnethylene-4t, 9j-decadienal which is obtained and 318 mg (1.0 mmol) of the phosphorane Ill, (a-formyl-ethylidene)-triphenyl-phosphorane, are dissolved in 5 ml of benzene. The solution is boiled at reflux for 40 hours,the benzene is thereupon sucked off, the residue treated with pentane, the precipitated phosphine oxide filtered off and the pentane again evaporated. The residual oil is distilled. There are thus obtained 161 mg (75percent) of gas-chromatographically pure trans B-sinensal l Va (2,6-dimethyl-l0 methylene-2t,6t, ll-dodecatrienal) of approximate boiling point lO0/0.l mm; n 1.0577; lR-bands at 1700 s, 1600 w, 900 s cm.

The phosphorane Ill (melting point 220-222) can be obtained as follows: Ethyl iodide is reacted in benzene with triphenyl-phosphine to give ethyltriphenyl-phosphonium iodide, and this is brought to reaction with butyl-lithium and formic acid methyl.

EXAMPLE 3 To a solution of 3.3 g (9.2 mmol) of (a-carbethoxyethylidine)-triphenyl-phosphorane in 15 ml hy ne hler de -Ls .1 mm l) qf4- t methylene-4t, 9 -decadienal are added at 20 and the mixture is kept for 60 hours at this temperature. The solvent is subsequently sucked off, hexane is added to the residue and the precipitated triphenylphosineoxide is filtered off; the solvent is evaporated from the filtrate and the residue distilled in the bulb tube. There are obtained 1.24 g (78 percent) of a colorless oil, b.p. l00/0.l mm. A semple of this oil is chromatographed on a 100 fold amount of silicagel (Merck 0.050.2 mm). With benzene the pure 2.6-dimethylmethylene-2t,6t,1l-dodecatrienoic acid ethyl ester is eluted. n 1.5009. 1R bonds at 1725s, l650w, l600m, 900s.

100 mg of anhydrous aluminiumchloride (0.75 mmol) and 95 mg (2.35 mmol)of lithiumaluminiumhydride are suspended in 3 ml of absolute ether. 170 mg of 2.6-dimethyl-10-methylene-2t,6t,l ldodecatrienoic acid ethyl ester, dissolved in a small amount of ether are pipetted to the above mixture at 80 under exclusion of humidity. The mixture is stirred for minutes at 30, then cooled again to 80, and about 0.5 ml of methanol are added. The mixture is poured on ice/0.1 n hydrochloric acid and then follows extraction with ether. The etherical layer is washed neutral with water and then dried over sodiumsulfate. The ether is distilled off and the residual oil distilled in the bulb tube. 189 mg (83 percent) of 2.6- dimethyll 0-methylene-2t,6t-l l-dodecatrienol are obtained, b.p. l00/0.1 mm. u 1.5083. IR-bands at 33005, 1660 w, 1640 vw, 1600s. 9005.

140 mg of MnO are suspended in 1 ml of hexane and 40 mg (0.18 mmol) of 2.6-dimethyl-IO-methylene-Z t,6t-1l-do-decatrienol are added to this mixture. The reaction mixture is stirred for 21 hours at room ,temperature under nitrogen. The MnO is separated by filtration of the reaction mixture through Celite and the hexane is sucked off from the filtrate. The residue is distilled in the bulb tube, thereby 19 mg (48 percent) of trans-B-sinensal are obtained; b.p. 100/0.l mm.

EXAMPLE 4 19 mg (0.5 mmol) of sodiumborohydride are dis-I olved in 1 ml of a mixture of waterlmethanol= 1:1 and a solution of 168 mg (1 mmol) of 4-methyl-8- methylene-4t,9-decadienal in 1 ml of methanol is added slowly at 0 to the former solution. The reaction mixture is kept for 3.5 hours at room temperature. The reaction mixture is worked up by adding ether to it, then shaking the resulting solution twice with l n acetic acid, then washing it with sodiumbicarbonate and finally with water until neutral. The etherical layer is dried over sodium sulfate, the solvent is evaporated and the residue distilled in the bulb tube. 170 mg (100 percent) of 4-methyl-8-methylene-4t-9-decadienol are obtained; b.p. l00/0.1 mm. lR-bands at 3330s, 1610m, 905s.

The foregoing illustrates the practice of this invention, which however, is not to be limited thereby but is to be construed as broadly as permissible in view of the prior art and limited solely by the appended claims.

What is claimed is:

1. The process which comprises ozonizing a compound having the formula:

with not more than 1 mole equivalent of ozone per mole of said compound, at temperatures below room temperature and decomposing the ozonization product in the presence of a reducing agent suitable for reducing ozonization products to aldehydes, to form an aldehyde having the formula 

2. The process of claim 1 wherein the starting material is selected from the group consisting of trans Alpha -farnesene, Beta -farnesene and a mixture of Alpha -farnesene and Beta -farnesene. 